Rowe Stevie, Siegel David, Benjamin Daniel K
Department of Pediatrics, Duke University, Durham, North Carolina.
Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
Clin Ther. 2015 Sep 1;37(9):1924-32. doi: 10.1016/j.clinthera.2015.08.006. Epub 2015 Aug 29.
Approximately 1 of 6 children in the United States is obese. This has important implications for drug dosing and safety because pharmacokinetic (PK) changes are known to occur in obesity due to altered body composition and physiologic mechanisms. Inappropriate drug dosing in an emergency setting can limit therapeutic efficacy and increase drug-related toxic effects for obese children. Few systematic reviews examining PK properties and drug dosing in obese children have been performed.
We identified 25 emergency care drugs from the Strategic National Stockpile and Acute Care Supportive Drugs List and performed a systematic review for each drug in 3 study populations: obese children (2-18 years of age), normal weight children, and obese adults (aged >18 years). For each study population, we first reviewed a drug's Food and Drug Administration label and then performed a systematic literature review. From the literature, we extracted drug PK data, biochemical properties, and dosing information. We then reviewed data in 3 age subpopulations (2-7 years, 8-12 years, and 13-18 years) for obese and normal weight children and by route of drug administration (intramuscular, intravenous, oral, and inhaled). If sufficient PK data were not available by age and route of administration, a data gap was identified.
Only 2 of 25 emergency care drugs (8%) contained dosing information on the Food and Drug Administration label for obese children and adults compared with 22 of 25 (88%) for normal weight children. We found no sufficient PK data in the literature for any of the emergency care drugs in obese children. Sufficient PK data were found for 7 of 25 emergency care drugs (28%) in normal weight children and 3 of 25 (12%) in obese adults.
Insufficient information exists to guide dosing in obese children for any of the emergency care drugs reviewed. This knowledge gap is alarming, given the known PK changes that occur in the setting of obesity. Future clinical trials examining the PK properties of emergency care medications in obese children should be prioritized.
在美国，约六分之一的儿童肥胖。这对药物剂量和安全性具有重要影响，因为已知肥胖会因身体组成和生理机制的改变而导致药代动力学（PK）变化。在紧急情况下，不适当的药物剂量会限制治疗效果，并增加肥胖儿童药物相关的毒性作用。很少有系统评价研究肥胖儿童的PK特性和药物剂量。
我们从国家战略储备和急性护理支持药物清单中确定了25种急救药物，并在3个研究人群中对每种药物进行了系统评价：肥胖儿童（2至18岁）、正常体重儿童和肥胖成人（年龄>18岁）。对于每个研究人群，我们首先查阅了药物的美国食品药品监督管理局（FDA）标签，然后进行了系统的文献综述。从文献中，我们提取了药物PK数据、生化特性和剂量信息。然后，我们针对肥胖和正常体重儿童的3个年龄亚组（2至7岁、8至12岁和13至18岁）以及药物给药途径（肌肉注射、静脉注射、口服和吸入）对数据进行了综述。如果按年龄和给药途径没有足够的PK数据，则确定存在数据缺口。
25种急救药物中，只有2种（8%）在FDA标签上包含了肥胖儿童和成人的剂量信息，而正常体重儿童为25种中的22种（88%）。我们在文献中未发现任何肥胖儿童急救药物有足够的PK数据。在正常体重儿童中，25种急救药物中有7种（28%）有足够的PK数据，在肥胖成人中为25种中的3种（12%）。
对于所审查的任何急救药物，都没有足够的信息来指导肥胖儿童的给药。鉴于肥胖情况下已知的PK变化，这一知识缺口令人担忧。应优先开展未来的临床试验，研究肥胖儿童急救药物的PK特性。
